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Schizophrenia: A Consequence of Gene-Environment Interactions?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195312 Year: Pages: 126 DOI: 10.3389/978-2-88919-531-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors (e.g. stress and cannabis use). In recent years, an increasing number of researchers worldwide have started investigating the ‘two-hit hypothesis’ of schizophrenia predicting that genetic and environmental risk factors interactively cause the development of the disorder. This work is starting to produce valuable new animal models and reveal novel insights into the pathophysiology of schizophrenia. Eventually, it might help advance studies of the molecular pathways involved in this mental disorder and propose more specific molecular medicine. However, the complexity of this multi-factorial line of research has also caused difficulties in data interpretation and comparison. Our research topic is intended to cover past and current directions in research dedicated to the understanding and measurement of gene-environment interactions (GxE) in schizophrenia, the neurobiological and behavioural consequences of such interactions as well as the challenges and limitations one encounters when working on complex aetiological systems.

Habituation mechanisms and their impact on cognitive function

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194629 Year: Pages: 110 DOI: 10.3389/978-2-88919-462-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Habituation describes the progressive decrease of the amplitude or frequency of a motor response to repeated sensory stimulation that is not caused by sensory receptor adaptation or motor fatigue. Habituation can occur in different time scales: habituation within a testing session has been termed short-term habituation, whereas habituation across testing sessions has been termed long-term habituation. Generally, the more spaced the stimuli for inducing habituation are presented (i.e. the slower habituation is induced), the longer it seems to take to recover the behavioural response to its initial magnitude. Habituation is opposed by behavioural sensitization, which is thought to be an independent mechanism that leads to an increased behavioural response, especially if the sensory stimulus is annoying or aversive. Habituation provides an important mechanism for filtering sensory information, as it allows filtering out irrelevant stimuli and thereby focussing on important stimuli, a prerequisite for many cognitive tasks. The importance is demonstrated in mental disorders that are associated with disruptions in habituation, e.g. schizophrenia and autism spectrum disorders. The inability to filter out irrelevant information in patients with these disorders strongly correlates with disruptions in higher cognitive functions, such as in different types of memory and attention. Habituation is also considered to be the most basic form of non-associative implicit learning, and it can be observed throughout the animal kingdom. Based on the importance of habituation for cognitive function and therefore for the survival of an animal, it is assumed that habituation mechanisms are highly conserved across species. On the other hand, there is emerging evidence for a multitude of homo- and heterosynaptic mechanisms underlying habituation, depending on the modality of sensory stimulation, the level of sensory information processing where habituation occurs, and the temporal composition of sensory stimulation. Eric Kandel used the sea hare Aplysia in order to study habituation mechanisms of the gill withdrawal reflex; however, the molecular mechanisms remain largely elusive to date. A multitude of different organisms, behaviours, and experimental approaches have been used since in order to study habituation, but still surprisingly little is known about the underlying mechanisms. New insights also come from an unexpected side: in the recent past, groups that have been studying molecular mechanisms underlying short- and long-term synaptic plasticity phenomenons in different parts of the rodent brain are starting to link these plasticity processes to behavioural habituation. The scope of this Frontier Research Topic is to give an overview over the concept of habituation, different animal and behavioural models used for studying habituation mechanisms, as well as the different synaptic and molecular processes suggested to play a role in behavioural habituation through Original Research Articles, Methods, Hypothesis & Theory Articles, and Reviews.

Cognitive deficits in schizophrenia and other neuropsychiatric disorders: Convergence of preclinical and clinical evidence

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196791 Year: Pages: 283 DOI: 10.3389/978-2-88919-679-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-08-16 10:34:25
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Neuropsychiatric diseases, such as schizophrenia, Alzheimer's disease, and etc., represent a serious medical and socioeconomic problems. These diseases are often accompanied by impairments of cognitive function, e.g., abstract thinking, decision-making, attention, and several types of memory. Such deficits significantly disrupt quality of life and daily functioning of patients. Cognitive deficits in neuropsychiatric diseases are associated with alterations of brain morphology and function, and are often resistant to therapeutic interventions. In schizophrenia and related disorders, cognitive deficits are also defined as endophenotypes, i.e. measurable phenotypes linking these disaeses with discrete heritable and reproducible traits. This points to the importance of elucidating these endophenotypes in translational studies. Animal models may not mimic the full spectrum of clinical symptoms, but may act as analogies of particular behaviors or other pathological outcomes. They are useful to search for the etiology of particular psychiatric illnesses and novel therapeutics. Moreover, several behavioral tests to measure cognitive performance in rodents and other species have been implemented. The primary focus of the present topic is to provide up-to-date information on cognitive deficits of neuropsychiatric disorders, such as schizophrenia. This Research Topic also delineates future directions for translational studies aimed at developing novel treatments/interventions of cognitive disturbances.

Breaking the cycle: Attacking the malaria parasite in the liver

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196951 Year: Pages: 173 DOI: 10.3389/978-2-88919-695-1 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General) --- Microbiology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Despite significant progress in the global fight against malaria, this parasitic infection is still responsible for nearly 300 million clinical cases and more than half a million deaths each year, predominantly in African children less than 5 years of age. The infection starts when mosquitoes transmit small numbers of parasites into the skin. From here, the parasites travel with the bloodstream to the liver where they undergo an initial round of replication and maturation to the next developmental stage that infects red blood cells. A vaccine capable of blocking the clinically silent liver phase of the Plasmodium life cycle would prevent the subsequent symptomatic phase of this tropical disease, including its frequently fatal manifestations such as severe anemia, acute lung injury, and cerebral malaria. Parasitologists, immunologists, and vaccinologists have come to appreciate the complexity of the adaptive immune response against the liver stages of this deadly parasite. Lymphocytes play a central role in the elimination of Plasmodium infected hepatocytes, both in humans and animal models, but our understanding of the exact cellular interactions and molecular effector mechanisms that lead to parasite killing within the complex hepatic microenvironment of an immune host is still rudimentary. Nevertheless, recent collaborative efforts have led to promising vaccine approaches based on liver stages that have conferred sterile immunity in humans – the University of Oxford's Ad prime / MVA boost vaccine, the Naval Medical Research Center’s DNA prime / Ad boost vaccine, Sanaria Inc.'s radiation-attenuated whole sporozoite vaccine, and Radboud University Medical Centre’s and Sanaria's derived chemoprophylaxis with sporozoites vaccines. The aim of this Research Topic is to bring together researchers with expertise in malariology, immunology, hepatology, antigen discovery and vaccine development to provide a better understanding of the basic biology of Plasmodium in the liver and the host’s innate and adaptive immune responses. Understanding the conditions required to generate complete protection in a vaccinated individual will bring us closer to our ultimate goal, namely to develop a safe, scalable, and affordable malaria vaccine capable of inducing sustained high-level protective immunity in the large proportion of the world’s population constantly at risk of malaria.

The Physiological Functions of the Amyloid Precursor Protein Gene Family

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453559 Year: Pages: 275 DOI: 10.3389/978-2-88945-355-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:45
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The amyloid precursor protein APP plays a key role in the pathogenesis of Alzheimer’s disease (AD), as proteolytical cleavage of APP gives rise to the Aß peptide which is deposited in the brains of Alzheimer patients. Despite this, our knowledge of the normal cell biological and physiological functions of APP and the closely related APLPs is limited. This may have hampered our understanding of AD, since evidence has accumulated that not only the production of the Aß peptide but also the loss of APP-mediated functions may contribute to AD pathogenesis. Thus, it appears timely and highly relevant to elucidate the functions of the APP gene family from the molecular level to their role in the intact organism, i.e. in the context of nervous system development, synapse formation and adult synapse function, as well as neural homeostasis and aging. Why is our understanding of the APP functions so limited? APP and the APLPs are multifunctional proteins that undergo complex proteolytical processing. They give rise to an almost bewildering array of different fragments that may each subserve specific functions. While Aß is aggregation prone and neurotoxic, the large secreted ectodomain APPsa - produced in the non-amyloidogenic a-secretase pathway - has been shown to be neurotrophic, neuroprotective and relevant for synaptic plasticity, learning and memory. Recently, novel APP cleavage pathways and enzymes have been discovered that have gained much attention not only with respect to AD but also regarding their role in normal brain physiology. In addition to the various cleavage products, there is also solid evidence that APP family proteins mediate important functions as transmembrane cell surface molecules, most notably in synaptic adhesion and cell surface signaling. Elucidating in more detail the molecular mechanisms underlying these divers functions thus calls for an interdisciplinary approach ranging from the structural level to the analysis in model organisms. Thus, in this research topic of Frontiers we compile reviews and original studies, covering our current knowledge of the physiological functions of this intriguing and medically important protein family.

Metal Metabolism in Animals

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ISBN: 9783038428435 9783038428442 Year: Pages: X, 356 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2018-04-20 14:25:48
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Through evolution of life, animals have adapted to the ubiquitous presence of metals in the biosphere. They utilize the more frequent ones as essential constituents of their biochemical machinery. In fact, about 40% of all proteins present in animal cells are so-called metalloproteins. On the other hand, animals have invented regulatory and detoxifying mechanisms to protect themselves from critical concentrations of both essential and non-essential metal concentrations. Metallomics is a modern approach applying cellular, biochemical, molecular and analytical methods to investigate the relationships of metals in their cellular context. The present edition contains a number of original articles and reviews dealing with various aspects of metallomics in animals, published as Special Issues of the International Journal of Molecular Sciences in 2016 and 2017. The book addresses subjects such as metal definition in biology, metabolism of metals in invertebrate and vertebrate animals, metal detoxification and regulation strategies, supplementation of essential trace elements, metal behavior in pregnancy and embryonic development, as well as metal toxicology and emerging medical implications.

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